The authors revised this Rapid Response at BMJ's request in line with BMJ's Terms and Conditions for Rapid Responses.
Dear Editor,
In the article ‘Anomalies in the review process and interpretation of the evidence in the NICE guideline for chronic fatigue syndrome and myalgic encephalomyelitis’ published in the Journal of Neurology, Neurosurgery & Psychiatry on 10th July 2023, the authors claim NICE invented a new definition of ME. These claims are unfounded as NICE used the Institute of Medicine (IOM) criteria which is now 8 years old and was created using a more robust process than many other definitions as it drew on samples from different countries and compared the most widely used definitions of ME.
One area where NICE felt there was a gap in the IOM criteria was the lack of an empirical process alongside other methods. Leonard Jason's four-item empiric criteria were the only criteria that used adequate empiric methods, and this aligned very closely with the IOM criteria. As a result, NICE operationalised the IOM criteria for use in the NHS, with the four-item criteria helping to substantiate their approach.
NICE does not measure a trial’s success based on the researchers’ own terms but by analysing the raw data and applying the committee's agreed protocol. This allows NICE to measure whether a treatment had an effect or not. This is striking when looking at the assertion that research showed that the favoured treatment...
The authors revised this Rapid Response at BMJ's request in line with BMJ's Terms and Conditions for Rapid Responses.
Dear Editor,
In the article ‘Anomalies in the review process and interpretation of the evidence in the NICE guideline for chronic fatigue syndrome and myalgic encephalomyelitis’ published in the Journal of Neurology, Neurosurgery & Psychiatry on 10th July 2023, the authors claim NICE invented a new definition of ME. These claims are unfounded as NICE used the Institute of Medicine (IOM) criteria which is now 8 years old and was created using a more robust process than many other definitions as it drew on samples from different countries and compared the most widely used definitions of ME.
One area where NICE felt there was a gap in the IOM criteria was the lack of an empirical process alongside other methods. Leonard Jason's four-item empiric criteria were the only criteria that used adequate empiric methods, and this aligned very closely with the IOM criteria. As a result, NICE operationalised the IOM criteria for use in the NHS, with the four-item criteria helping to substantiate their approach.
NICE does not measure a trial’s success based on the researchers’ own terms but by analysing the raw data and applying the committee's agreed protocol. This allows NICE to measure whether a treatment had an effect or not. This is striking when looking at the assertion that research showed that the favoured treatments of CBT and GET were safe, when, in reality, safety data either was not collected or was incomplete or uninterpretable. These treatments have led to many complaints from people with ME that they were harmful and led to deterioration. This was illustrated in the MEAction UK 2019 report, ME services in the UK Not Fit For Purpose.
The authors of this critique also claim that NICE didn't aggregate data properly, but there are hundreds of pages of meta-analysis proving they were meticulous and gave detailed consideration to every trial they looked at. The real complaint here seems to be that NICE didn't aggregate data in the way the authors of this paper wish they had. For example, the Cochrane review of exercise in ME, which many of these authors favour, pools results from multiple different interventions with very different protocols, and this has been argued to provide an evidence base for GET by extension. But that would be like pooling the evidence for CBT, DBT, ABA, psychoanalysis and counselling, and then claiming this proves ABA alone is effective. NICE sensibly grouped "like with like", so that trials with similar protocols were grouped together, improving the accuracy and specificity of their analysis.
The criticism that NICE gave too much weight to survey evidence, and the lived experience of people with ME, was factored into the committee's decisions alongside other evidence. ‘NICE considers all types of evidence in its evaluations. This includes evidence from published and unpublished data, data from non-UK sources, databases of ongoing clinical trials, end-to-end studies, conference proceedings, and data from registries, real-world evidence and other observational sources.’
The complaint that energy management isn't evidenced is bizarre. Energy management isn't offered as a therapy and it isn't curative. It is essentially the same as the activity management of the last guideline - which many of the same authors were happy to accept when they contributed to that guideline. Energy management is essentially a continuation of those same principles of care but it is not offered or presented as a treatment. The Forward ME group of charities has also endorsed this approach.
With regard to GET and whether fixed increments in activity were required, NICE had to look at the evidence from the trials. Numerous trials refer to increments that are fixed and shouldn't be changed except with the approval of the clinician. The PACE manual for therapists explains that GET is based on the deconditioning model and discourages reductions in exercise when in a crash, ‘A central concept of GET is to MAINTAIN exercise as much as possible during a CFS/ME setback. This is to reduce the many negative consequences of rest, and to allow the body to habituate to the increase in activity. If activity and exercise is reduced at this time, the boom/bust cycle continues, and the body is not able to desensitise to the increase in activity: which is, of course, an essential component of a graded increase in exercise and activity.’ If the treatment was delivered in a different way in practice it would indicate that the GET as researched wasn’t effective in clinical settings.
Similarly, it cannot be merely assumed that because one approach is helpful elsewhere, that it is helpful here. There is no treatment that is suitable for all diseases. Chronic primary pain isn't ME and asthma isn't diabetes and it should be self-evident that different illnesses need different treatments.
We are also concerned that news coverage about this paper (and previous news coverage quoting the same authors) continues to paint people with ME as unreliable witnesses to their own illness and lives. This is a long-standing form of bias against disabled people.
In conclusion, this article reads as an attack on the 2021 NICE guideline for ME/CFS by a group of researchers who have focussed on treating ME with Graded Exercise Therapy and CBT. By contrast, the patient community welcomes the NICE guideline and the robust review of the evidence that NICE carried out. The guideline is a real improvement on the previous version and the removal of Graded Exercise Therapy as a recommended treatment was greeted with relief. It is now time for researchers and medical staff to work with people living with ME to implement the NICE guideline throughout the NHS. Further delay and obstruction will cause more harm and increase the suffering of a very vulnerable group of people.
Dear Editor,
I am writing to express my appreciation for the enlightening article titled "Childbirth Delivery Mode and the Risk of Multiple Sclerosis: A Prospective Population-Based Study" [1] recently published in your esteemed journal. The study, which examines the potential relationship between childbirth mode and the subsequent risk of multiple sclerosis (MS) development, presents a comprehensive analysis and incites intriguing discussions. The authors embarked on a commendable endeavor by conducting a meticulous prospective cohort study encompassing individuals born in Norway between 1967 and 2003. Their investigation aimed to unravel the potential influence of caesarean section (CS) births on the risk of adult-onset MS. The findings unveil an association suggesting an 18% elevated risk of MS among individuals born via CS, as compared to those born vaginally, after considering an array of confounding factors. However, the authors astutely highlight that this association does not persist when a sibling-matched analysis is undertaken. Furthermore, this intriguing connection appears to be primarily confined to individuals born preterm or via emergency CS. Such nuanced insights underline the complexities underlying the childbirth mode and MS risk paradigm, necessitating a thoughtful interpretation of the findings.
The authors acknowledge the divergent findings from previous studies, emphasizing the discrepancies between their results and those report...
Dear Editor,
I am writing to express my appreciation for the enlightening article titled "Childbirth Delivery Mode and the Risk of Multiple Sclerosis: A Prospective Population-Based Study" [1] recently published in your esteemed journal. The study, which examines the potential relationship between childbirth mode and the subsequent risk of multiple sclerosis (MS) development, presents a comprehensive analysis and incites intriguing discussions. The authors embarked on a commendable endeavor by conducting a meticulous prospective cohort study encompassing individuals born in Norway between 1967 and 2003. Their investigation aimed to unravel the potential influence of caesarean section (CS) births on the risk of adult-onset MS. The findings unveil an association suggesting an 18% elevated risk of MS among individuals born via CS, as compared to those born vaginally, after considering an array of confounding factors. However, the authors astutely highlight that this association does not persist when a sibling-matched analysis is undertaken. Furthermore, this intriguing connection appears to be primarily confined to individuals born preterm or via emergency CS. Such nuanced insights underline the complexities underlying the childbirth mode and MS risk paradigm, necessitating a thoughtful interpretation of the findings.
The authors acknowledge the divergent findings from previous studies, emphasizing the discrepancies between their results and those reported in an Iranian case–control study. This retrospective analysis, while reporting a substantial increase in MS risk among individuals born by CS, utilized self-reported data and was susceptible to potential biases [2]. The contrast between this study and a Danish nationwide cohort study also warrants consideration [3]. In both studies, similar estimates were observed when adjusting for pertinent factors, indicating a convergence of findings.
The study delves into intriguing potential mechanisms underlying the observed associations. The authors propose that alterations in gut microbiota, delayed immune system development, and differential cytokine responses may underpin the relationship between CS births and MS risk. The exploration of these pathways adds a layer of depth to the investigation, urging further research into the intricate interplay between childbirth experiences and immune-mediated diseases.
While the study boasts numerous strengths, such as its large population-based cohort, prospective design, and verification of MS cases by neurologists, the authors candidly delineate its limitations. The lack of generalizability to other populations due to the exclusive focus on Norwegian individuals is acknowledged, as is the absence of maternal smoking information for certain cohorts. Despite these limitations, the sibling-matched analyses and comprehensive data integration fortify the study's robustness.
In conclusion, the study "Childbirth Delivery Mode and the Risk of Multiple Sclerosis: A Prospective Population-Based Study" significantly advances our understanding of the intricate relationship between childbirth mode and MS risk. The authors' astute exploration of potential mechanisms, combined with the meticulous consideration of confounding factors, highlights the need for cautious interpretation. The association identified between CS births and MS risk, particularly in subgroups with complicated pregnancies, beckons further investigation into the underlying confounders shaping this relationship. This study underscores the importance of ongoing research into the nexus between early life experiences and long-term health outcomes, contributing valuable insights into our understanding of immune-mediated diseases.
Thank you for providing a platform for this thought-provoking study, and I look forward to witnessing future advancements in this evolving field.
References
1. Akash, K., et al., Childbirth delivery mode and the risk of multiple sclerosis: a prospective population-based study. Journal of Neurology, Neurosurgery & Psychiatry, 2023: p. jnnp-2023-331241.
2. Maghzi, A.H., et al., Cesarean delivery may increase the risk of multiple sclerosis. Mult Scler, 2012. 18(4): p. 468-71.
3. Nielsen, N.M., et al., Cesarean section and offspring's risk of multiple sclerosis: a Danish nationwide cohort study. Mult Scler, 2013. 19(11): p. 1473-7.
I recently had the opportunity to read your article titled "Prognostic Value of Spinal Cord Lesion Measures in Early Relapsing-Remitting Multiple Sclerosis" [1] and I want to extend my appreciation for the significant contribution your research has made to the field of multiple sclerosis (MS). Your study investigated the relation of whole spinal cord lesion number (SCLN) and volume (SCLV) to the future occurrence and type of confirmed disability accumulation (CDA) in patients with relapsing-remitting MS. The manual delineation of SC lesions and the subsequent analyses provided valuable insights into the prospective value of these measures in predicting clinical outcomes. The significant association between the absence of SC lesions and reduced CDA risk suggests the importance of SC lesions as a prognostic indicator in MS. Additionally, the close correlation between SCLN and SCLV, and their independent association with CDA, provide further support for the relevance of these measures in predicting disability accumulation.
The classification of CDA events into progression independent of relapse activity (PIRA) and relapse-associated worsening (RAW) facilitated a nuanced analysis of their association with SC lesion measures. The significant association with PIRA, but not RAW, hints at distinct underlying mechanisms for different types of disability progression, which could have implications for treatment strategies.
While your study provides valuable insi...
I recently had the opportunity to read your article titled "Prognostic Value of Spinal Cord Lesion Measures in Early Relapsing-Remitting Multiple Sclerosis" [1] and I want to extend my appreciation for the significant contribution your research has made to the field of multiple sclerosis (MS). Your study investigated the relation of whole spinal cord lesion number (SCLN) and volume (SCLV) to the future occurrence and type of confirmed disability accumulation (CDA) in patients with relapsing-remitting MS. The manual delineation of SC lesions and the subsequent analyses provided valuable insights into the prospective value of these measures in predicting clinical outcomes. The significant association between the absence of SC lesions and reduced CDA risk suggests the importance of SC lesions as a prognostic indicator in MS. Additionally, the close correlation between SCLN and SCLV, and their independent association with CDA, provide further support for the relevance of these measures in predicting disability accumulation.
The classification of CDA events into progression independent of relapse activity (PIRA) and relapse-associated worsening (RAW) facilitated a nuanced analysis of their association with SC lesion measures. The significant association with PIRA, but not RAW, hints at distinct underlying mechanisms for different types of disability progression, which could have implications for treatment strategies.
While your study provides valuable insights, I also acknowledge the limitations you outlined. A prospective design, although challenging, would have strengthened the study's findings. Furthermore, the relatively low number of patients with disability worsening necessitated classifying only the first CDA event, limiting the exploration of potential later events and subsequent subgroup analyses. The use of three different MRI scanners might have increased data heterogeneity, but it also enhanced the generalizability of the results.
Differentiating between symptomatic and asymptomatic SC lesions and considering the potential benefits of using 3D gradient-recalled echo sequences for lesion detection could have further enriched the study's findings.
Notwithstanding these limitations, your research is a valuable addition to the existing literature on MS prognostication. Your findings hold promise for improving patient care by providing clinicians with valuable prognostic information to guide treatment decisions.
Once again, I commend you and your team for your excellent work. Your dedication to advancing our understanding of multiple sclerosis is commendable, and I look forward to seeing how your research progresses in the future.
References
1. Markus L, Julian M, Matthias B, et al. Prognostic value of spinal cord lesion measures in early relapsing-remitting multiple sclerosis. Journal of Neurology, Neurosurgery & Psychiatry. 2023:jnnp-2023-331799. doi: 10.1136/jnnp-2023-331799.
There are several shortcomings in the commentary by White et al. For brevity, this response focuses on four main points.
1. New case definition
In the past 20 years, multiple case definitions have been published that require post-exertional malaise (PEM) as a core feature of ME/CFS, such as the Canadian Consensus Criteria (CCC), International Consensus Criteria (ICC), and the Institute of Medicine (IOM) criteria. NICE’s definition is based on the latter.
These case definitions are the ones used in research and clinical practice today. White et al. refer to the 1994 criteria developed by the Centers for Disease Control and Prevention (CDC) but the CDC no longer seems to use this case definition. Instead, they advise healthcare providers to diagnose ME/CFS using the IOM criteria where PEM is a required symptom.
NICE evaluated scientific evidence for ME/CFS as it is currently defined and not for a case definition that was published nearly 30 years ago. Other reviews on ME/CFS, such as the recent one by IQWIG in Germany, have used a similar approach. (1)
It is incorrect to state that NICE “downgraded nearly thirty years of research.” The previous NICE guidance from 2007 on ME/CFS already highlighted PEM as a core feature of ME/CFS, and studies that used this description were not downgraded in the evidence review. Neither were studies that used the CCC, ICC, or IOM criteria mentioned above.
There are several shortcomings in the commentary by White et al. For brevity, this response focuses on four main points.
1. New case definition
In the past 20 years, multiple case definitions have been published that require post-exertional malaise (PEM) as a core feature of ME/CFS, such as the Canadian Consensus Criteria (CCC), International Consensus Criteria (ICC), and the Institute of Medicine (IOM) criteria. NICE’s definition is based on the latter.
These case definitions are the ones used in research and clinical practice today. White et al. refer to the 1994 criteria developed by the Centers for Disease Control and Prevention (CDC) but the CDC no longer seems to use this case definition. Instead, they advise healthcare providers to diagnose ME/CFS using the IOM criteria where PEM is a required symptom.
NICE evaluated scientific evidence for ME/CFS as it is currently defined and not for a case definition that was published nearly 30 years ago. Other reviews on ME/CFS, such as the recent one by IQWIG in Germany, have used a similar approach. (1)
It is incorrect to state that NICE “downgraded nearly thirty years of research.” The previous NICE guidance from 2007 on ME/CFS already highlighted PEM as a core feature of ME/CFS, and studies that used this description were not downgraded in the evidence review. Neither were studies that used the CCC, ICC, or IOM criteria mentioned above.
2. Blinding and subjective outcomes
White et al. write: “The NICE committee decided to downgrade all fatigue outcomes based on the premise that it is a subjective measure.” This is incorrect. Fatigue outcomes in studies with a low risk of bias such as the double-blind Rituximab trial were not downgraded.
NICE did downgrade quality of evidence when subjective outcomes (not just fatigue, but also pain, sleep, quality of life, etc.) were used in trials where participants and therapists were not blinded as this combination creates a high risk of bias. This grading is in accordance with the Cochrane Handbook which states that “the potential for bias cannot be ignored even if the outcome assessor cannot be blinded." (2) In the case of patient-reported outcome measures such as fatigue, the Cochrane Handbook considers patients to be the outcome assessor.
Moreover, trials of GET and CBT also included objective measurements such as fitness tests, actigraphy, and employment data and these indicated no clinically relevant improvements. (3)
3. Long-term follow-up
The largest studies on GET and CBT — the PACE (4) and GETSET (5) trials — failed to find significant benefits of these interventions at their longest follow-up. This suggests that initial improvements might be due to response bias or a placebo effect. It is questionable to recommend treatments if the long-term follow-up shows no benefit.
In both GETSET and PACE, a sensitivity analysis indicated that additional treatment received after randomization was unlikely to explain the null results. The authors of GETSET reported that “there is no evidence that the improvements observed in the SMC group were due to them having received more exposure to therapy than the GES group after trial completion.” (5) Similarly, in the PACE trial the control group caught up on the intervention group and “there was some evidence from an exploratory analysis that improvement after the 1-year trial final outcome was not associated with receipt of additional treatment with CBT or GET.” (4)
4. Harms
The Cochrane review on GET included only randomized trials but concluded: “We are uncertain about the risk of serious adverse reactions because the certainty of the evidence is very low.” (6) There was too little data on adverse effects to form a conclusion.
Surveys and qualitative studies, on the other hand, have consistently found a negative impact of GET on some ME/CFS patients. This has been reported for several decades, in multiple countries, and with little indication that harms are due to improper implementation of GET. (7) Considering the adage ‘primum non nocere’, it is sensible to use a lower threshold for evaluating evidence on the potential harms of a medical intervention compared with its potential benefits.
At the NICE Roundtable Discussion prior to Guideline release (8), health profession stakeholders had ample opportunity to raise concerns. Following clear, succinct responses from a representative of the committee, consistent with our comments above, no further objections were raised.
2. Higgins JPT, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, et al. Cochrane Handbook for Systematic Reviews of Interventions. 2nd Edition. Chichester (UK): John Wiley & Sons; 2019.
3. Vink M, Vink-Niese A. Graded exercise therapy for myalgic encephalomyelitis/chronic fatigue syndrome is not effective and unsafe. Re-analysis of a Cochrane review. Health Psychol Open. 2018 Dec;5(2):2055102918805187.
4. Sharpe M, Goldsmith KA, Johnson AL, Chalder T, Walker J, White PD. Rehabilitative treatments for chronic fatigue syndrome: long-term follow-up from the PACE trial. Lancet Psychiatry. 2015 Dec 1;2(12):1067–74.
5. Clark LV, McCrone P, Pesola F, Vergara-Williamson M, White PD. Guided graded exercise self-help for chronic fatigue syndrome: Long term follow up and cost-effectiveness following the GETSET trial. J Psychosom Res. 2021 Jul 1;146:110484.
7. Geraghty K, Hann M, Kurtev S. Myalgic encephalomyelitis/chronic fatigue syndrome patients’ reports of symptom changes following cognitive behavioural therapy, graded exercise therapy and pacing treatments: Analysis of a primary survey compared with secondary surveys. J Health Psychol. 2019 Sep;24(10):1318–33.
Ayton et al. reported the association between ferritin, apolipoprotein E (APOE) and dementia-related biomarkers such as amyloid β42/total-tau and phosphorylated tau181 (p-tau181) in cerebrospinal fluid (CSF) (1). CSF ferritin and APOE were positively associated with p-tau181, which was most predominant in subjects without increase in amyloid β42/total-tau. I present information about the study.
Pan et al. investigated the associations of CSF ferritin and CSF biomarkers of Alzheimer's disease (AD) (2). They found that CSF ferritin increased in subjects with more advanced categories of CSF biomarkers such as amyloid β42 and p-pau, although there were stronger relationships of CSF ferritin with p-tau and t-tau, rather than amyloid β42. This means that biological action of ferritin in the brain for AD may be more closely related to tau protein.
Baringer et al. described brain iron homeostasis in Alzheimer's disease, Parkinson's disease, and other neurodegenerative diseases (3). They emphasized that endothelial cells of the blood-brain barrier were the site of iron transport regulation, and iron uptake, transcytosis, and release were mainly conducted. By controlling the excess of brain iron, neurodegenerative disorders may be improved. The mechanism that tau protein spreads through functionally connected neurons in Alzheimer's disease have been precisely reported (4), and it may be related to the excess of brain iron storage.
Ayton et al. reported the association between ferritin, apolipoprotein E (APOE) and dementia-related biomarkers such as amyloid β42/total-tau and phosphorylated tau181 (p-tau181) in cerebrospinal fluid (CSF) (1). CSF ferritin and APOE were positively associated with p-tau181, which was most predominant in subjects without increase in amyloid β42/total-tau. I present information about the study.
Pan et al. investigated the associations of CSF ferritin and CSF biomarkers of Alzheimer's disease (AD) (2). They found that CSF ferritin increased in subjects with more advanced categories of CSF biomarkers such as amyloid β42 and p-pau, although there were stronger relationships of CSF ferritin with p-tau and t-tau, rather than amyloid β42. This means that biological action of ferritin in the brain for AD may be more closely related to tau protein.
Baringer et al. described brain iron homeostasis in Alzheimer's disease, Parkinson's disease, and other neurodegenerative diseases (3). They emphasized that endothelial cells of the blood-brain barrier were the site of iron transport regulation, and iron uptake, transcytosis, and release were mainly conducted. By controlling the excess of brain iron, neurodegenerative disorders may be improved. The mechanism that tau protein spreads through functionally connected neurons in Alzheimer's disease have been precisely reported (4), and it may be related to the excess of brain iron storage.
References
1. Ayton S, Janelidze S, Kalinowski P, et al. CSF ferritin in the clinicopathological progression of Alzheimer's disease and associations with APOE and inflammation biomarkers. J Neurol Neurosurg Psychiatry 2023;94(3):211-219.
2. Pan R, Luo S, Huang Q, et al. The associations of cerebrospinal fluid ferritin with neurodegeneration and neuroinflammation along the Alzheimer's Disease Continuum. J Alzheimers Dis 2022;88(3):1115-1125.
3. Baringer SL, Simpson IA, Connor JR. Brain iron acquisition: An overview of homeostatic regulation and disease dysregulation. J Neurochem 2023;165(5):625-642.
4. Schoonhoven DN, Coomans EM, Millán AP, et al. Tau protein spreads through functionally connected neurons in Alzheimer's disease: a combined MEG/PET study. Brain 2023. doi: 10.1093/brain/awad189
In “Functional neurological disorder is a feminist issue” by McLoughlin et al.,[1] authors explain that FND patients “suffer subtle and overt forms of discrimination”, suggesting that “FND clinical services and research are chronically underfunded in line with the neglect of disorders disproportionately affecting women”. Ultimately, they insist that feminists should support “parity of esteem” for FND with other neurological conditions.
I suggest that the idea of an alliance between feminism and FND is highly problematic. First, authors minimize the seriousness of human rights violations against women in the name of hysteria. Second, they fail to consider the role that FND plays in healthcare gender bias across specialties. Third, they perpetuate the myth that functional diagnosis rarely errs, further threatening women’s safety in the healthcare system.
First, while authors do acknowledge “objectification and exploitation” of women diagnosed with hysteria, their concern is merely that “some sociologists and scientists have opined that the diagnosis was used as a ‘patriarchal tool’ to silence or ignore complaints of women”. There’s no mention of sexualization of women’s symptoms in the name of hysteria, even as recently as ICD-10, or the range of sexual treatments to which “hysterical” women have been subjected, including genital mutilation. There’s no acknowledgment that these treatments, like sectioning based on the wishes of husbands, fathers, or sons, are...
In “Functional neurological disorder is a feminist issue” by McLoughlin et al.,[1] authors explain that FND patients “suffer subtle and overt forms of discrimination”, suggesting that “FND clinical services and research are chronically underfunded in line with the neglect of disorders disproportionately affecting women”. Ultimately, they insist that feminists should support “parity of esteem” for FND with other neurological conditions.
I suggest that the idea of an alliance between feminism and FND is highly problematic. First, authors minimize the seriousness of human rights violations against women in the name of hysteria. Second, they fail to consider the role that FND plays in healthcare gender bias across specialties. Third, they perpetuate the myth that functional diagnosis rarely errs, further threatening women’s safety in the healthcare system.
First, while authors do acknowledge “objectification and exploitation” of women diagnosed with hysteria, their concern is merely that “some sociologists and scientists have opined that the diagnosis was used as a ‘patriarchal tool’ to silence or ignore complaints of women”. There’s no mention of sexualization of women’s symptoms in the name of hysteria, even as recently as ICD-10, or the range of sexual treatments to which “hysterical” women have been subjected, including genital mutilation. There’s no acknowledgment that these treatments, like sectioning based on the wishes of husbands, fathers, or sons, are violations of human rights perpetrated into the 1960s.
Most importantly, there’s not a word about the many millions of women with disease mistakenly attributed to hysteria, their suffering, or their deaths, without medical care or support. Women with lupus, endometriosis, heart disease, multiple sclerosis, myasthenia gravis, women who resist sex with husbands, gay women, sex workers, and women resistant to housework and caring for children – all of these were gathered under the rubric of hysteria and forced into “moral treatment” based on the wisdom of their male doctors. Authors of this article do their best to obfuscate the firm lineage from hysteria to FND, and the explicit insistence of current FND researchers that “the disappearance of hysteria is an illusion”.[2] These omissions, all on their own, should lead to serious concern for feminists.
Second, authors fail to consider the role that FND plays in the problem of healthcare gender bias. Without hesitation they state that 70% of those with FND are women, a figure outstripped only by somatic symptom disorder, with an astonishing 10:1 recommended female-to-male ratio.[3] Unfortunately, there exists no research that attempts to evaluate gender imbalance in these diagnoses in a way that’s free of bias. Instead, research unanimously evaluates what doctors in fact do when it comes to diagnosis of FND in women vs men. Findings of this kind tell us only that doctors do what they’ve been trained to do for centuries, diagnosing psychosomatic conditions predominantly in women. No substantial research has attempted to determine whether it’s actually wise to see FND in this gendered way.
There is abundant evidence that gender imbalance in diagnosis of functional disorders and SSD is unsupported, because it’s clear now that women struggle to access the tests, treatments, and referrals that men readily receive in the same circumstances. Findings of this kind are well known. Women with symptoms of heart disease are far more likely to be diagnosed with a mental health condition. We receive less hyperperfusion therapy for stroke, and we wait longer for it. We’re more likely to receive sedatives when we need pain medication, and women’s diseases, like endometriosis and lupus, have appallingly long diagnostic delays. Clearly clinicians take it for granted that psychosomatic conditions are an everyday problem for women. As a new label for hysteria, one that in no way rejects the original construct, FND contributes substantially to that impression. Indeed, most clinicians are aware that new hysteria labels have been devised, at least in part, to mislead women into compliance with treatment.[4]
Third, authors affirm the idea that misdiagnosis of FND is rare, citing the well-known finding that “the proportion of misdiagnosis was less than 4%”.[5] What they don’t say is that central studies on misdiagnosis of conversion/FND do not determine error rate. They determine the rate at which doctors are willing to imagine that the diagnosis has erred, confirming the error with findings, and noting results for the record. Slater’s studies on misdiagnosis of hysteria in the 1960s took a more scientific approach, with direct effort to uncover unrecognized disease in a large group of patients diagnosed with hysteria. These methods are not comparable. Low revision rates are not cause for celebration. They’re cause for concern that while error in psychosomatic diagnosis is very common – as evidenced by women’s routine difficulty accessing the healthcare they need – once the diagnosis is made, doctors are dangerously unwilling to imagine that it might be mistaken.
From a feminist perspective, “parity of esteem with neurological conditions of equivalent epidemiological and economic importance” is not warranted for FND. When FND research disclaims hysteria for violations of women’s human rights, when researchers are actively engaged in reversing healthcare gender injustice, and when studies on error seriously commit to reducing mistaken denial of healthcare to women, then it will be time to give FND more attention. Until then, no one should mistake funding for FND with an investment in gender health equity. It is hard to imagine a construct more directly opposed to the aims of feminism.
[1] McLoughlin C, Hoeritzauer I, Cabreira V, et al. Functional neurological disorder is a feminist issue [published online ahead of print, 2023 Mar 28]. J Neurol Neurosurg Psychiatry. 2023;jnnp-2022-330192.
[2] Stone J, Hewett R, Carson A, Warlow C, Sharpe M. The 'disappearance' of hysteria: historical mystery or illusion? J R Soc Med. 2008;101(1):12-8.
[4] Sharpe M, Carson A. "Unexplained" somatic symptoms, functional syndromes, and somatization: do we need a paradigm shift? Ann Intern Med. 2001;134(9 Pt 2):926-930.
[5] Stone J, Smyth R, Carson A, et al. Systematic review of misdiagnosis of conversion symptoms and hysteria. BMJ 2005;331:989.
Dear Editor-in-Chief,
We read with great interest the consensus guidelines for diagnosis and management of spontaneous intracranial hypotension (SIH). [1] In the absence of any recommendations, this guideline will help clinicians in formulating their diagnostic and management approaches for SIH. In this letter, we wish to discuss about the epidural blood patch (EBP) in the management of SIH. The role of targeted EBP for management of SIH has not been compared with non-targeted EBP in randomized controlled trials to establish superiority of one over the other. A recent systematic review of studies with 10 or more patients with SIH reported similar success with either technique. [2] However, where expertise is available and when the precise site of cerebrospinal fluid (CSF) leak is identifiable, it is prudent to consider targeted EBP as the first choice. This reduces the volume of autologous blood required, minimizes the need of reliance on gravity for spread of epidurally placed blood to the potential site of leak and decreases the procedure failure rates and need for subsequent EBPs or surgical interventions. In our center, which is a tertiary care neurosciences academic hospital, after an initial conservative management for a week, a targeted EBP is performed as the preferred approach to manage SIH. [3] If the site of leak is not determinable and if the expertise to perform cervical or thoracic EBP is not available, a non-targeted EBP may be the preferred interventi...
Dear Editor-in-Chief,
We read with great interest the consensus guidelines for diagnosis and management of spontaneous intracranial hypotension (SIH). [1] In the absence of any recommendations, this guideline will help clinicians in formulating their diagnostic and management approaches for SIH. In this letter, we wish to discuss about the epidural blood patch (EBP) in the management of SIH. The role of targeted EBP for management of SIH has not been compared with non-targeted EBP in randomized controlled trials to establish superiority of one over the other. A recent systematic review of studies with 10 or more patients with SIH reported similar success with either technique. [2] However, where expertise is available and when the precise site of cerebrospinal fluid (CSF) leak is identifiable, it is prudent to consider targeted EBP as the first choice. This reduces the volume of autologous blood required, minimizes the need of reliance on gravity for spread of epidurally placed blood to the potential site of leak and decreases the procedure failure rates and need for subsequent EBPs or surgical interventions. In our center, which is a tertiary care neurosciences academic hospital, after an initial conservative management for a week, a targeted EBP is performed as the preferred approach to manage SIH. [3] If the site of leak is not determinable and if the expertise to perform cervical or thoracic EBP is not available, a non-targeted EBP may be the preferred intervention. [4]
The second point that remains unclear and poses management dilemma is the treatment approach when a patient is diagnosed with SIH and also manifests with a subdural hematoma (SDH) causing intracranial mass effect. The clinical picture is confusing when the orthostatic nature of headache, classical of SIH, changes to a continuous headache pattern due to SDH. Here, if the SIH is treated first with an EBP, possibility of increase in intracranial pressure adding to that due to a SDH is likely. On the contrary, if SDH is evacuated first, there is possibility of recollection due to ongoing CSF leak. There is need for more clarity on the appropriate approach in such a scenario.
References
1. Cheema S, Anderson J, Angus-Leppan H, et alMultidisciplinary consensus guideline for the diagnosis and management of spontaneous intracranial hypotensionJournal of Neurology, Neurosurgery & Psychiatry Published Online First: 05 May 2023. doi: 10.1136/jnnp-2023-331166
2. D'Antona L, Jaime Merchan MA, Vassiliou A, Watkins LD, Davagnanam I, Toma AK, Matharu MS. Clinical Presentation, Investigation Findings, and Treatment Outcomes of Spontaneous Intracranial Hypotension Syndrome: A Systematic Review and Meta-analysis. JAMA Neurol. 2021;78(3):329-337.
3. Sriganesh K, Saini J, Bhadrinarayan V. Targeted cervical epidural blood patch for the management of refractory headache in a patient with spontaneous intracranial hypotension. J Neurosurg Anesthesiol. 2015;27(1):68-9
4. Shukla D, Sadashiva N, Saini J, Kamath S. Spontaneous Intracranial Hypotension - A Dilemma. Neurol India. 2021;69(Supplement):S456-S462.
Åkerstedt et al. conducted a case-control study with 2075 cases and 3164 controls to investigate the association between sleep and risk of multiple sclerosis (MS) (1). Sleep duration, circadian disruption and sleep quality during adolescence were used for sleep variables. The authors calculated the adjusted OR with 95% CIs using logistic regression models, and short sleep (<7 hours/night) and low sleep quality were significantly associated with increased risk of developing MS. I have a question regarding the ways of multivariate analysis.
The ratio in the number of cases and controls is about 1.5 in this study. If the authors selected unconditional logistic regression analysis, OR might become conservative. If the authors selected conditional logistic regression analysis, the increased number of controls is preferable to make stable estimation. Instead of selecting a case-control study with a matching procedure, using all pooled data without a matching procedure can be selected for the analysis (2).
Anyway, a recall method has a possibility of including bias and risk assessment of MS with subjective sleep variables should be paid with caution.
References
1. Åkerstedt T, Olsson T, Alfredsson L, et al. Insufficient sleep during adolescence and risk of multiple sclerosis: results from a Swedish case-control study. J Neurol Neurosurg Psychiatry 2023;94(5):331-6.
2. Hamajima N, Hirose K, Inoue M, et al. Case-control studies: matched controls...
Åkerstedt et al. conducted a case-control study with 2075 cases and 3164 controls to investigate the association between sleep and risk of multiple sclerosis (MS) (1). Sleep duration, circadian disruption and sleep quality during adolescence were used for sleep variables. The authors calculated the adjusted OR with 95% CIs using logistic regression models, and short sleep (<7 hours/night) and low sleep quality were significantly associated with increased risk of developing MS. I have a question regarding the ways of multivariate analysis.
The ratio in the number of cases and controls is about 1.5 in this study. If the authors selected unconditional logistic regression analysis, OR might become conservative. If the authors selected conditional logistic regression analysis, the increased number of controls is preferable to make stable estimation. Instead of selecting a case-control study with a matching procedure, using all pooled data without a matching procedure can be selected for the analysis (2).
Anyway, a recall method has a possibility of including bias and risk assessment of MS with subjective sleep variables should be paid with caution.
References
1. Åkerstedt T, Olsson T, Alfredsson L, et al. Insufficient sleep during adolescence and risk of multiple sclerosis: results from a Swedish case-control study. J Neurol Neurosurg Psychiatry 2023;94(5):331-6.
2. Hamajima N, Hirose K, Inoue M, et al. Case-control studies: matched controls or all available controls? J Clin Epidemiol 1994;47(9):971-5.
We are writing to respectfully offer some additional comments on the recent publication of Hannaway et al. in JNNP titled “Visual dysfunction is a better predictor than retinal thickness for dementia in Parkinson’s disease”.
While the authors provided interesting insights on the predictive value of higher order visual functions for dementia, we noticed that the authors did not find significant associations between parafoveal GCIPL (pfGCIPL) and cognition in their work, whereas our research did. As they mentioned, the range of cognitive impairment was higher in our sample, and possibly this might have driven our findings. However, we would like to add that the relationship between the retina and cognition is not linear, according to our data. As such, we calculated relative risks by categorizing continuous variables, which allowed us to identify non-linear relationships between pfGCIPL and cognitive impairment. Furthermore, we speculate that these variables do not exhibit a synchronous pattern of change over time, suggesting that the temporal trends are not closely linked, which might justify the lack of association in the current work.
We do agree with the authors in that visual function is a good predictor of cognitive deterioration. Our previous work also demonstrated this fact, but we would like to highlight the benefits of retinal OCT imaging in this context, if its utility is validated. Retinal OCT imaging is a faster and easier-to-measure technique com...
We are writing to respectfully offer some additional comments on the recent publication of Hannaway et al. in JNNP titled “Visual dysfunction is a better predictor than retinal thickness for dementia in Parkinson’s disease”.
While the authors provided interesting insights on the predictive value of higher order visual functions for dementia, we noticed that the authors did not find significant associations between parafoveal GCIPL (pfGCIPL) and cognition in their work, whereas our research did. As they mentioned, the range of cognitive impairment was higher in our sample, and possibly this might have driven our findings. However, we would like to add that the relationship between the retina and cognition is not linear, according to our data. As such, we calculated relative risks by categorizing continuous variables, which allowed us to identify non-linear relationships between pfGCIPL and cognitive impairment. Furthermore, we speculate that these variables do not exhibit a synchronous pattern of change over time, suggesting that the temporal trends are not closely linked, which might justify the lack of association in the current work.
We do agree with the authors in that visual function is a good predictor of cognitive deterioration. Our previous work also demonstrated this fact, but we would like to highlight the benefits of retinal OCT imaging in this context, if its utility is validated. Retinal OCT imaging is a faster and easier-to-measure technique compared to measuring visual functions. Moreover, OCTs are widely available in most ophthalmology departments, and this accessibility makes it a practical tool for assessing cognitive impairment and predicting dementia risk, particularly in primary care settings where time and resources are often limited. Furthermore, OCT might be also useful to be incorporated in clinical trials of disease-modifying therapies, as it allows objective, reliable and quantitative measurements of retinal parameters. All these advantages make it imperative to explore and better understand the temporal relationship between the retina and cognition.
We would like to address some final points that were discussed in the paper to provide further clarification. In our work, we included carriers with E46K mutation in the SNCA gene, not GBA gene. Also, the authors state that it is not clear whether model that tested the association between baseline pfGCIPL thickness and the risk of cognitive decline in idiopathic PD was adjusted for age. In fact, the model was adjusted for age, but also for disease duration, sex and levodopa equivalent daily dose.
To conclude, we are grateful for the valuable insights provided by the authors about the usefulness of the retina for cognitive monitoring. Moving forward, we remain committed to further exploring and elucidating this fascinating area of research, and we share the authors' enthusiasm for advancing our knowledge on the temporal dynamics of the retinal structure and its relationship with cognitive processes.
Functional neurological disorder is an important aspect with respect to burden and cost of management irrespective of gender as the authors have pointed out very rightly1.
It can be chronic but most of the times present as an emergency therby increasing panic, inpatient admissions. Smooth care, workup and appropriate guidelines for the same may help a lot in such conditions.
There is limited information, awareness, health care utilities, and economic burden of such patients which makes the situation more grim.
So there should be multidisciplinary approach i.e. physiotherapy, occupational therapy, speech and language therapy, and psychological assessment. Functional neurological disorders overlap with refractory neurological conditions i.e. headache, seizure, focal deficit etc., so better these patients be subdivided in these categories. Framing universal guidelines all across the world according to subdivisions with appropriate line of care as is being done in various other disorders may help a lot to smoothen improve management and help reduce the cost of therapy and gender bias.
References-
1. Caoimhe McLoughlin, Ingrid Hoeritzauer, Verónica Cabreira et al. http://dx.doi.org/10.1136/jnnp-2022-330192
2. Christopher D. Stephen, Vicki Fung, Codrin I. Lungu et al Alberto J. Espay Assessment of Emergency Department and Inpatient Use and Costs in Adult and Pediatric Functional Neur...
Functional neurological disorder is an important aspect with respect to burden and cost of management irrespective of gender as the authors have pointed out very rightly1.
It can be chronic but most of the times present as an emergency therby increasing panic, inpatient admissions. Smooth care, workup and appropriate guidelines for the same may help a lot in such conditions.
There is limited information, awareness, health care utilities, and economic burden of such patients which makes the situation more grim.
So there should be multidisciplinary approach i.e. physiotherapy, occupational therapy, speech and language therapy, and psychological assessment. Functional neurological disorders overlap with refractory neurological conditions i.e. headache, seizure, focal deficit etc., so better these patients be subdivided in these categories. Framing universal guidelines all across the world according to subdivisions with appropriate line of care as is being done in various other disorders may help a lot to smoothen improve management and help reduce the cost of therapy and gender bias.
References-
1. Caoimhe McLoughlin, Ingrid Hoeritzauer, Verónica Cabreira et al. http://dx.doi.org/10.1136/jnnp-2022-330192
2. Christopher D. Stephen, Vicki Fung, Codrin I. Lungu et al Alberto J. Espay Assessment of Emergency Department and Inpatient Use and Costs in Adult and Pediatric Functional Neurological Disorders. JAMA Neurol. 2021;78(1):88-101. doi:10.1001/jamaneurol.2020.3753
The authors revised this Rapid Response at BMJ's request in line with BMJ's Terms and Conditions for Rapid Responses.
Dear Editor,
Show MoreIn the article ‘Anomalies in the review process and interpretation of the evidence in the NICE guideline for chronic fatigue syndrome and myalgic encephalomyelitis’ published in the Journal of Neurology, Neurosurgery & Psychiatry on 10th July 2023, the authors claim NICE invented a new definition of ME. These claims are unfounded as NICE used the Institute of Medicine (IOM) criteria which is now 8 years old and was created using a more robust process than many other definitions as it drew on samples from different countries and compared the most widely used definitions of ME.
One area where NICE felt there was a gap in the IOM criteria was the lack of an empirical process alongside other methods. Leonard Jason's four-item empiric criteria were the only criteria that used adequate empiric methods, and this aligned very closely with the IOM criteria. As a result, NICE operationalised the IOM criteria for use in the NHS, with the four-item criteria helping to substantiate their approach.
NICE does not measure a trial’s success based on the researchers’ own terms but by analysing the raw data and applying the committee's agreed protocol. This allows NICE to measure whether a treatment had an effect or not. This is striking when looking at the assertion that research showed that the favoured treatment...
Dear Editor,
Show MoreI am writing to express my appreciation for the enlightening article titled "Childbirth Delivery Mode and the Risk of Multiple Sclerosis: A Prospective Population-Based Study" [1] recently published in your esteemed journal. The study, which examines the potential relationship between childbirth mode and the subsequent risk of multiple sclerosis (MS) development, presents a comprehensive analysis and incites intriguing discussions. The authors embarked on a commendable endeavor by conducting a meticulous prospective cohort study encompassing individuals born in Norway between 1967 and 2003. Their investigation aimed to unravel the potential influence of caesarean section (CS) births on the risk of adult-onset MS. The findings unveil an association suggesting an 18% elevated risk of MS among individuals born via CS, as compared to those born vaginally, after considering an array of confounding factors. However, the authors astutely highlight that this association does not persist when a sibling-matched analysis is undertaken. Furthermore, this intriguing connection appears to be primarily confined to individuals born preterm or via emergency CS. Such nuanced insights underline the complexities underlying the childbirth mode and MS risk paradigm, necessitating a thoughtful interpretation of the findings.
The authors acknowledge the divergent findings from previous studies, emphasizing the discrepancies between their results and those report...
I recently had the opportunity to read your article titled "Prognostic Value of Spinal Cord Lesion Measures in Early Relapsing-Remitting Multiple Sclerosis" [1] and I want to extend my appreciation for the significant contribution your research has made to the field of multiple sclerosis (MS). Your study investigated the relation of whole spinal cord lesion number (SCLN) and volume (SCLV) to the future occurrence and type of confirmed disability accumulation (CDA) in patients with relapsing-remitting MS. The manual delineation of SC lesions and the subsequent analyses provided valuable insights into the prospective value of these measures in predicting clinical outcomes. The significant association between the absence of SC lesions and reduced CDA risk suggests the importance of SC lesions as a prognostic indicator in MS. Additionally, the close correlation between SCLN and SCLV, and their independent association with CDA, provide further support for the relevance of these measures in predicting disability accumulation.
Show MoreThe classification of CDA events into progression independent of relapse activity (PIRA) and relapse-associated worsening (RAW) facilitated a nuanced analysis of their association with SC lesion measures. The significant association with PIRA, but not RAW, hints at distinct underlying mechanisms for different types of disability progression, which could have implications for treatment strategies.
While your study provides valuable insi...
There are several shortcomings in the commentary by White et al. For brevity, this response focuses on four main points.
1. New case definition
In the past 20 years, multiple case definitions have been published that require post-exertional malaise (PEM) as a core feature of ME/CFS, such as the Canadian Consensus Criteria (CCC), International Consensus Criteria (ICC), and the Institute of Medicine (IOM) criteria. NICE’s definition is based on the latter.
These case definitions are the ones used in research and clinical practice today. White et al. refer to the 1994 criteria developed by the Centers for Disease Control and Prevention (CDC) but the CDC no longer seems to use this case definition. Instead, they advise healthcare providers to diagnose ME/CFS using the IOM criteria where PEM is a required symptom.
NICE evaluated scientific evidence for ME/CFS as it is currently defined and not for a case definition that was published nearly 30 years ago. Other reviews on ME/CFS, such as the recent one by IQWIG in Germany, have used a similar approach. (1)
It is incorrect to state that NICE “downgraded nearly thirty years of research.” The previous NICE guidance from 2007 on ME/CFS already highlighted PEM as a core feature of ME/CFS, and studies that used this description were not downgraded in the evidence review. Neither were studies that used the CCC, ICC, or IOM criteria mentioned above.
2. Blinding and subjective outcomes
Show MoreWhite...
Ayton et al. reported the association between ferritin, apolipoprotein E (APOE) and dementia-related biomarkers such as amyloid β42/total-tau and phosphorylated tau181 (p-tau181) in cerebrospinal fluid (CSF) (1). CSF ferritin and APOE were positively associated with p-tau181, which was most predominant in subjects without increase in amyloid β42/total-tau. I present information about the study.
Pan et al. investigated the associations of CSF ferritin and CSF biomarkers of Alzheimer's disease (AD) (2). They found that CSF ferritin increased in subjects with more advanced categories of CSF biomarkers such as amyloid β42 and p-pau, although there were stronger relationships of CSF ferritin with p-tau and t-tau, rather than amyloid β42. This means that biological action of ferritin in the brain for AD may be more closely related to tau protein.
Baringer et al. described brain iron homeostasis in Alzheimer's disease, Parkinson's disease, and other neurodegenerative diseases (3). They emphasized that endothelial cells of the blood-brain barrier were the site of iron transport regulation, and iron uptake, transcytosis, and release were mainly conducted. By controlling the excess of brain iron, neurodegenerative disorders may be improved. The mechanism that tau protein spreads through functionally connected neurons in Alzheimer's disease have been precisely reported (4), and it may be related to the excess of brain iron storage.
References...
Show MoreIn “Functional neurological disorder is a feminist issue” by McLoughlin et al.,[1] authors explain that FND patients “suffer subtle and overt forms of discrimination”, suggesting that “FND clinical services and research are chronically underfunded in line with the neglect of disorders disproportionately affecting women”. Ultimately, they insist that feminists should support “parity of esteem” for FND with other neurological conditions.
I suggest that the idea of an alliance between feminism and FND is highly problematic. First, authors minimize the seriousness of human rights violations against women in the name of hysteria. Second, they fail to consider the role that FND plays in healthcare gender bias across specialties. Third, they perpetuate the myth that functional diagnosis rarely errs, further threatening women’s safety in the healthcare system.
First, while authors do acknowledge “objectification and exploitation” of women diagnosed with hysteria, their concern is merely that “some sociologists and scientists have opined that the diagnosis was used as a ‘patriarchal tool’ to silence or ignore complaints of women”. There’s no mention of sexualization of women’s symptoms in the name of hysteria, even as recently as ICD-10, or the range of sexual treatments to which “hysterical” women have been subjected, including genital mutilation. There’s no acknowledgment that these treatments, like sectioning based on the wishes of husbands, fathers, or sons, are...
Show MoreDear Editor-in-Chief,
Show MoreWe read with great interest the consensus guidelines for diagnosis and management of spontaneous intracranial hypotension (SIH). [1] In the absence of any recommendations, this guideline will help clinicians in formulating their diagnostic and management approaches for SIH. In this letter, we wish to discuss about the epidural blood patch (EBP) in the management of SIH. The role of targeted EBP for management of SIH has not been compared with non-targeted EBP in randomized controlled trials to establish superiority of one over the other. A recent systematic review of studies with 10 or more patients with SIH reported similar success with either technique. [2] However, where expertise is available and when the precise site of cerebrospinal fluid (CSF) leak is identifiable, it is prudent to consider targeted EBP as the first choice. This reduces the volume of autologous blood required, minimizes the need of reliance on gravity for spread of epidurally placed blood to the potential site of leak and decreases the procedure failure rates and need for subsequent EBPs or surgical interventions. In our center, which is a tertiary care neurosciences academic hospital, after an initial conservative management for a week, a targeted EBP is performed as the preferred approach to manage SIH. [3] If the site of leak is not determinable and if the expertise to perform cervical or thoracic EBP is not available, a non-targeted EBP may be the preferred interventi...
Åkerstedt et al. conducted a case-control study with 2075 cases and 3164 controls to investigate the association between sleep and risk of multiple sclerosis (MS) (1). Sleep duration, circadian disruption and sleep quality during adolescence were used for sleep variables. The authors calculated the adjusted OR with 95% CIs using logistic regression models, and short sleep (<7 hours/night) and low sleep quality were significantly associated with increased risk of developing MS. I have a question regarding the ways of multivariate analysis.
The ratio in the number of cases and controls is about 1.5 in this study. If the authors selected unconditional logistic regression analysis, OR might become conservative. If the authors selected conditional logistic regression analysis, the increased number of controls is preferable to make stable estimation. Instead of selecting a case-control study with a matching procedure, using all pooled data without a matching procedure can be selected for the analysis (2).
Anyway, a recall method has a possibility of including bias and risk assessment of MS with subjective sleep variables should be paid with caution.
References
Show More1. Åkerstedt T, Olsson T, Alfredsson L, et al. Insufficient sleep during adolescence and risk of multiple sclerosis: results from a Swedish case-control study. J Neurol Neurosurg Psychiatry 2023;94(5):331-6.
2. Hamajima N, Hirose K, Inoue M, et al. Case-control studies: matched controls...
We are writing to respectfully offer some additional comments on the recent publication of Hannaway et al. in JNNP titled “Visual dysfunction is a better predictor than retinal thickness for dementia in Parkinson’s disease”.
While the authors provided interesting insights on the predictive value of higher order visual functions for dementia, we noticed that the authors did not find significant associations between parafoveal GCIPL (pfGCIPL) and cognition in their work, whereas our research did. As they mentioned, the range of cognitive impairment was higher in our sample, and possibly this might have driven our findings. However, we would like to add that the relationship between the retina and cognition is not linear, according to our data. As such, we calculated relative risks by categorizing continuous variables, which allowed us to identify non-linear relationships between pfGCIPL and cognitive impairment. Furthermore, we speculate that these variables do not exhibit a synchronous pattern of change over time, suggesting that the temporal trends are not closely linked, which might justify the lack of association in the current work.
We do agree with the authors in that visual function is a good predictor of cognitive deterioration. Our previous work also demonstrated this fact, but we would like to highlight the benefits of retinal OCT imaging in this context, if its utility is validated. Retinal OCT imaging is a faster and easier-to-measure technique com...
Show MoreFunctional neurological disorder is an important aspect with respect to burden and cost of management irrespective of gender as the authors have pointed out very rightly1.
Show MoreIt can be chronic but most of the times present as an emergency therby increasing panic, inpatient admissions. Smooth care, workup and appropriate guidelines for the same may help a lot in such conditions.
There is limited information, awareness, health care utilities, and economic burden of such patients which makes the situation more grim.
So there should be multidisciplinary approach i.e. physiotherapy, occupational therapy, speech and language therapy, and psychological assessment. Functional neurological disorders overlap with refractory neurological conditions i.e. headache, seizure, focal deficit etc., so better these patients be subdivided in these categories. Framing universal guidelines all across the world according to subdivisions with appropriate line of care as is being done in various other disorders may help a lot to smoothen improve management and help reduce the cost of therapy and gender bias.
References-
1. Caoimhe McLoughlin, Ingrid Hoeritzauer, Verónica Cabreira et al. http://dx.doi.org/10.1136/jnnp-2022-330192
2. Christopher D. Stephen, Vicki Fung, Codrin I. Lungu et al Alberto J. Espay Assessment of Emergency Department and Inpatient Use and Costs in Adult and Pediatric Functional Neur...
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